{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T12:07:37Z","timestamp":1789560457521,"version":"build-2803163510"},"reference-count":46,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,1,8]],"date-time":"2025-01-08T00:00:00Z","timestamp":1736294400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,1,8]],"date-time":"2025-01-08T00:00:00Z","timestamp":1736294400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002367","name":"Chinese Academy of Sciences","doi-asserted-by":"publisher","award":["XDB39000000"],"award-info":[{"award-number":["XDB39000000"]}],"id":[{"id":"10.13039\/501100002367","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>We investigated the specific factors driving abnormal angiogenesis in Alzheimer's disease (AD) and its role in cerebrovascular lesions and neurodegeneration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      We assessed cerebrovascular pathologies, amyloid\u2010beta (A\u03b2), and tau pathologies in\n                      <jats:italic>post mortem<\/jats:italic>\n                      human brains and detected 12 angiogenic factors in cerebrospinal fluid (CSF) from the China Aging and Neurodegenerative Disease Initiative (CANDI) cohort.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>We observed severe blood\u2010brain barrier damage and elevated levels of the vascular marker CD31 in human AD brains, which had a stronger correlation with tau pathology than A\u03b2 pathology. Consistently, only CSF pTau181 showed positive associations with CSF angiogenesis factors (soluble vascular endothelial growth factor receptor 2 [sVEGFR2], VEGF\u2010C, VEGF\u2010D, placental growth factor [PLGF], Angiopoietin2, and Serpin E1), but not CSF A\u03b242\/40. Additionally, higher levels of CSF sVEGFR1, soluble Tyrosine\u2010protein kinase receptor 2 [sTIE2], PLGF, and interleukin 8 [IL8], as well as lower levels of CSF urokinase\u2010type plasminogen activator [uPA], were associated with worsen cerebrovascular pathologies and neurodegeneration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Our findings indicate that tau pathology may play a critical role in pathological angiogenesis, contributing to cerebrovascular lesions and neurodegeneration in AD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>HIGHLIGHTS<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>BBB damage and elevated vascular marker CD31 in human AD brains had a stronger correlation with tau pathology than A\u03b2 pathology.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>CSF pTau181 mediated the effect of CSF A\u03b242\/40 on CSF sVEGFR1 and sTIE2.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Only CSF pTau181 showed positive associations with sVEGFR2, VEGF\u2010C, VEGF\u2010D, PLGF, Angiopoietin2, and Serpin E1.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Higher sVEGFR1, sTIE2, PLGF, and IL8, and lower uPA in CSF, were associated with cerebrovascular pathologies and neurodegeneration.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  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